Effect of neoadjuvant chemotherapy on the clinical outcomes and immune microenvironment in oral squamous cell carcinoma

Neoadjuvant chemotherapy (NAC) is increasingly significant in oral squamous cell carcinoma (OSCC), but its effect on the immunological profile of OSCC is not well defined. This study aims to evaluate NAC's impact on OSCC patients and to characterize immune checkpoints and tumor-associated immune cells in tumor specimens before and after NAC. We compared the effects of NAC (16 cases) and surgery alone (18 cases) in OSCC treatment. Immunological markers were analyzed in tumor samples from 12 OSCC patients (6 with NAC, 6 without) using multiplex immunofluorescence. Two antibody panels were used to quantify markers, including POXPE3, CD4, CD8, CD68, PD-1, PD-L1, CTLA-4, CD66b, CD16, CD19, Caspase-3, and GSDMD. No significant difference in overall survival was observed between the NAC and control groups. NAC did not harm patients and led to downstaging in 8 individuals. CD8+PDL1+ expression increased significantly in NAC-treated cases (P < 0.05). Higher densities of PD1+, PDL1+, CTLA4+, and Caspase+ were found in NAC-OSCC. The density of CD8+PD1+, CD8+PDL1+, and CD68 + PDL1+ cells in the tumor was increased in NAC-treated cases. The densities of CD68⁺, CD16⁺, CD19⁺, CD66b+, and GSDMD + cells were lower in NAC-OSCC. NAC enhances clinical outcomes, reducing clinical stage and enabling more aggressive surgery, without causing harm. Increased CD8+PDL1+ cells in NAC-treated OSCC suggest that NAC may enhance immune response pathways, underscoring the need for further research into combining chemotherapy with immunotherapy in OSCC.